Is Extracorporeal Membrane Oxygenation a Panacea?

Extracorporeal membrane oxygenation (ECMO) has emerged as a vital life-support technique in critical care medicine, providing temporary circulatory and/or respiratory support for patients with severe cardiac or respiratory failure unresponsive to conventional therapies. This review aims to outline the importance of ECMO and provide a comprehensive overview of its main applications. Two primary types of ECMO, veno-arterial extracorporeal membrane oxygenation and veno-venous extracorporeal membrane oxygenation, serve distinct functions in supporting patients with cardiac or pulmonary dysfunction, respectively. While ECMO offers life-saving potential, its utilization requires careful consideration due to its cost and resource-intensiveness. Thus, a comprehensive evaluation of an individual patient’s clinical condition, prognosis, and potential for recovery is crucial. Ongoing research and technological advancements continually refine ECMO techniques, enhance patient selection criteria, and improve long-term outcomes. Within this narrative review, we present an updated approach to patient selection and ECMO utilization, supported by a detailed literature review. By consolidating the current evidence, we aim to provide healthcare professionals with valuable insights into the ECMO’s post-pandemic role.


Introduction
Mechanical cardiopulmonary support is commonly employed during both intraoperative and intensive care settings, particularly in cardiac surgery.However, sometimes cardiopulmonary support may be required in the intensive care unit.Extracorporeal membrane oxygenation (ECMO) or extracorporeal lung support (ECLS) serves as a life support system for providing prolonged cardiopulmonary assistance.Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and veno-venous extracorporeal membrane oxygenation (VV-ECMO) are 2 primary types of ECMO, offering respiratory support, with VA-ECMO additionally providing hemodynamic support.Since its inception in 1970, the ECMO experience has progressively expanded, gaining significant recognition. 1,2In this review, we comprehensively discuss the clinical advantages of ECMO, patient selection criteria, indications, contraindications, and its specific role in managing respiratory failure associated with viral pneumonia, which has become increasingly prevalent during the coronavirus disease 2019 (COVID-19) pandemic. 3Key studies are summarized in Table 1, and by incorporating an extensive review of available literature, our aim is to provide valuable insights and guidance for clinical practice in this evolving field.
Notably, neonates and children generally exhibit high survival rates following ECMO support for respiratory failure. 4Nevertheless, accurately estimating patient survival poses a challenge, as the mortality risk associated with this procedure is estimated to be approximately 50%.Typically, ECLS is considered when the risk of mortality reaches around 80%.To ensure a precise evaluation, the severity of the disease, likelihood of death, and organ failure are meticulously assessed, considering patient age and other factors. 5Complications may arise, some of which may result in significant morbidity.Extracorporeal membrane oxygenation-associated complications can be categorized as either device related, encompassing issues such as oxygenator malfunction, pump failure, circulatory blockages, and cannulation problems, or physiological, including Is Extracorporeal Membrane Oxygenation a Panacea?7][8][9] Initiation of ECMO triggers an inflammatory response akin to systemic inflammatory response syndrome. 101][12][13][14][15] Despite the escalating use of ECMO, our current understanding of the elicited inflammatory response remains limited.Patients supported with ECMO frequently exhibit an inflammatory response; however, a comprehensive understanding of the severe patient reactions to inflammation and their clinical trajectory is currently lacking.Further insight into this complex phenomenon is necessary to explore potential treatments and novel therapeutic strategies.

Techniques of Extracorporeal Membrane Oxygenation
Two ECMO techniques are commonly used (Figure 1):

Main Points
• We wrote this review to highlight the following main headings: • Extracorporeal membrane oxygenation (ECMO) is a life-saving medical intervention used in critical care, but it is not a universal cure-all solution.
• Extracorporeal membrane oxygenation provides mechanical support to patients with severe respiratory or circulatory failure when conventional treatments fail.
• While ECMO has shown remarkable success in certain cases, its efficacy varies depending on patient selection, timing, and underlying conditions.
• The decision to initiate ECMO should be carefully considered, and its benefits should be weighed against potential complications, including bleeding and infection.
• Extracorporeal membrane oxygenation's role in critical care highlights the need for a multidisciplinary approach, ongoing research, and strict protocols to optimize its use and improve patient outcomes.pump propels blood through the circuit, providing oxygenation and mechanical support to both the heart and lungs.The oxygenated blood is warmed to body temperature and returned to the patient via the venous cannula. 16,17

Hemostasis of Extracorporeal Membrane Oxygenation
Effective hemostasis management is a crucial aspect of ECMO therapy, as the use of anticoagulation to prevent clot formation within the circuit presents challenges in maintaining hemostasis.Achieving the delicate balance between preventing bleeding and minimizing thrombotic complications remains a constant concern.Close monitoring of coagulation parameters, such as activated clotting time or activated partial thromboplastin time, is essential for guiding anticoagulation therapy and detecting early signs of bleeding or clotting.
Collaborative efforts among the ECMO team, hematologists, and other specialists are vital to develop personalized hemostasis management strategies.These strategies may involve adjusting anticoagulation levels, employing antithrombotic agents, and implementing techniques to minimize circuit-related factors that contribute to coagulation activation.The goal is to maintain optimal hemostasis, prevent both bleeding and thrombotic complications, and ultimately improve patient outcomes during ECMO therapy. 18

Selecting the Perfect Candidate for Extracorporeal Membrane Oxygenation
Extracorporeal membrane oxygenation, a transformative technology with immense potential to save lives, necessitates cautious implementation to prevent additional harm to patients.Integration of ECMO within comprehensive clinical strategies, such as long-term platforms like ventricular assist devices and transplantation, becomes imperative, as it is not a viable standalone solution. 19The survival rates for patients who suffer out-of-hospital cardiac arrest (OHCA) remain alarmingly low.However, the use of ECMO in cases of cardiac arrest, known as extracorporeal cardiopulmonary resuscitation (ECPR), has demonstrated promising results in enhancing patient survival while preserving favorable neurological outcomes. 20A Danish study revealed a substantial failure rate, with only a minority of patients undergoing ECPR treatment achieving successful outcomes.Factors contributing to the avoidance of ECPR encompass prolonged prehospital low-flow duration, metabolic abnormalities, and diminished end-tidal carbon dioxide (ETCO 2 ) levels. 21

Indications
Patient selection and timing are crucial considerations in ECMO, with mortality rates rising with age and concomitant diseases. 22,23The use of scoring systems such as Respiratory ECMO Survival Prediction (RESP) and Murray scores can assist in the assessment.The RESP score predicts survival for ECMO patients, while the Murray score predicts mortality rates in the absence of ECMO.If ECMO is deemed necessary, prompt transfer to a specialized medical facility should be arranged. 24Clinical guidelines for Acute Respiratory Distress Syndrome (ARDS) recommend considering ECMO in adult patients with severe ARDS, supported by a moderate level of evidence (GRADE rating 2B).There are many experimental studies in the treatment of ARDS. 25,26Patients with severe hypoxemia or hypercapnia who do not respond to conventional lung-protective ventilation or adjunctive therapies should be referred to experts for guidance on ECMO indications and patient transport. 27][30][31][32][33] The CESAR study compared ECMO with standard ventilatory support in severe acute respiratory failure, revealing significantly higher 6-month survival without sequelae (63% vs. 47%) with ECMO, despite certain methodological limitations, including the study being conducted at a single center with specialized expertise in ECMO use. 34In the EOLIA study, early VV-ECMO versus delayed intervention in ARDS showed no statistically significant difference in 60-day mortality rates. 35][36] Veno-venous ECMO is recommended for adult patients with severe ARDS due to sepsis and failed mechanical ventilation, although quality of the evidence is low.Studies in England 37 and France 38 reported varied mortality rates for severe acute respiratory failure associated with influenza H1N1 patients transferred to ECMO centers.Extracorporeal membrane oxygenation may serve as a bridge to transplantation, benefiting some patients with chronic respiratory failure from interstitial lung disease. 39Evidence supporting VA-ECMO use for circulatory assistance in cardiogenic shock remains inadequate, as the ECMO-CS trial found no significant differences in clinical outcomes between immediate initiation and a conservative approach with delayed use. 40cent randomized trials suggest potential benefits of ECPR, yet evidence certainty is modest, and patients' selection criteria remain undetermined. 41Extracorporeal cardiopulmonary resuscitation in intra-hospital cardiac arrest (IHCA) shows low survival rates but favorable neurological outcomes at 1 year. 42Variables such as age, time of day, initial rhythm, medical history of renal failure, patient type (cardiac versus noncardiac and medical versus surgical), and duration of cardiac arrest influence IHCA causes and survival rates. 43Extracorporeal cardiopulmonary resuscitation is more effective in OHCA, 44 with early chest compression initiation improving pre-discharge rates. 45Implementing transportable VA-ECMO programs in hospitals allows treatment of critically ill patients with comparable survival rates. 468][49] Outof-hospital ECPR has been shown to be an effective 50 and economically acceptable pacing strategy. 513][54][55][56] Extracorporeal membrane oxygenation improves outcomes in AHCA cases, especially in acute hypothermiainduced cardiac arrest. 57Veno-arterial ECMO and endovascular therapy are rescue strategies for massive pulmonary embolism (PE) when thrombolysis is contraindicated, potentially aiding resuscitation in high-risk PE-related cardiac arrest. 58,59Immediate initiation of ECMO can potentially aid in resuscitation of patients with cardiac arrest due to high-risk PE. 60,61 Venoarterial ECMO and endovascular therapy are rescue strategies for massive PE when thrombolysis is contraindicated, potentially aiding resuscitation in high-risk PE-related cardiac arrest (57, 58).Successful VA-ECMO use has been reported in amniotic fluid embolism cases. 62,63Extracorporeal cardiopulmonary resuscitation indications in cancer patients are unclear, but understanding IHCA outcomes in this population is essential due to the incidence of cancer and improved survival rates. 64Venoarterial ECMO is a suitable treatment option for poisoning cases complicated by refractory cardiogenic shock or cardiac arrest, offering high survival rates with low complications. 65xtracorporeal membrane oxygenation may be indicated in severe status asthmaticus, 66 pheoc hromo cytom a-ind uced cardiomyopathy, 67,68 fulminant myocarditis, 69 ANCA-associated vasculitis, 70 and refractory thyroid storm. 71

Contraindications
Relative contraindications to ECMO include age older than 65 years, body mass index greater than 40, suppressed immunity, lack of a relative who can make medical decisions, and severe chronic systolic heart failure.There are certain contraindications to ECMO that should be considered, such as disseminated malignancy, severe deconditioning, uncontrolled bleeding, Adult patients with potentially reversible severe respiratory failure should be transferred to a specialized center with an ECMO-based management protocol.This recommendation applies to patients with a Murray score > 3.0 or pH level < 7.2 despite optimal conventional treatment.The goal is to improve survival rates and reduce the risk of severe disability.

Combes et al 33 2018 Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome
Among patients with very severe ARDS, 60-day mortality was not significantly lower with ECMO than with a strategy of conventional mechanical ventilation that included ECMO as rescue therapy.

Extracorporeal
Life Support Organization (ELSO) 5 2017 Guidelines for Cardiopulmonary Extracorporeal Life Support Organization This is a general guideline that consists of all indications and contraindications Schmidt et al 71 2015 Predicting survival after ECMO for refractory cardiogenic shock: the survival after veno-arterial-ECMO (SAVE)-score The study suggests that chronic renal failure, longer duration of ventilation prior to ECMO initiation, pre-ECMO organ failures, pre-ECMO cardiac arrest, congenital heart disease, lower pulse pressure, and lower serum bicarbonate (HCO 3 ) were risk factors associated with mortality.
Schmidt et al 72 2013 The PRESERVE mortality risk score and analysis of long-term outcomes after extracorporeal membrane oxygenation for severe acute respiratory distress syndrome Considering the potential for neurological injury, additional research is necessary to explore neuromonitoring protocols to enhance personalized anticoagulation management and improve survival rates in COVID-19 patients on ECMO. 96Given resource limitations, ECMO should be reserved for extremely severe cases of COVID-19 during a global pandemic. 97The utility of ECMO should be evaluated based on current circumstances, considering the need for specialized patient care and the capacity to manage a high volume of patients through centralization. 98

Conclusion
The utilization of VV-ECMO in the adult population has witnessed a significant global increase.Careful patient selection is paramount, ensuring that the etiology of respiratory failure in ARDS is reversible and unresponsive to conventional treatments while also considering formal contraindications to ECMO initiation.Furthermore, patients with irreversible diseases, such as end-stage lung disease, may be considered viable candidates for ECMO therapy, particularly when bridging toward lung transplantation.The employment of ECMO in the management of ARDS patients has demonstrated superior survival rates when compared to patients of similar age and disease severity who did not receive this advanced intervention.Nevertheless, it is noteworthy that the current body of literature addressing the use of VA-ECMO to support COVID-19 patients is sparse, necessitating further investigation to optimize its application and elucidate its potential benefits in this specific context.

Figure 1 .
Figure 1.The figure shows the 2different types of extracorporeal membrane oxygenation, the veno-atrial (VA) and the veno-venous (VV) systems.

Table 1 .
Respiratory Extracorporeal Membrane Oxygenation Survival Prediction Score Values for Calculation

Table 2 .
Literature Overview: Extracorporeal Life Support (Extracorporeal Membrane Oxygenation) Techniques, Indications, Contraindications, Complications, and Coronavirus Disease 2019 Considerations This study aims to describe patient characteristics in refractory cardiac arrest cases and explore reasons for refraining from ECPR treatment, providing insights into patient selection.Factors such as prolonged prehospital low-flow time, metabolic derangement, and low ETCO 2 were common reasons for abstaining from ECPR.considered for selected severe ARDS patients undergoing lung-protective ventilation, based on criteria such as a Murray Score >3 or pH <7.2 due to uncorrected hypercapnia.Additionally, factors like age, medical conditions, underlying ARDS causes, and ECMO availability should also be taken into account.
The objective of this study is to assess the effectiveness of the RESP score in predicting the survival rate of COVID-19 patients receiving VV-ECMO treatment during their hospital stay.
94LS to MCS was necessary for 3.1% of patients due to heart failure, myocarditis, or myocardial infarction.Survival rates for VV-ECLS and MCS were reported as 54.6% and 28.1%, respectively.94Anotherstudyevaluatedthe effectiveness of the RESP score (Table2) in predicting in-hospital survival in COVID-19 patients receiving VV-ECMO.However, the exclusive use of the RESP score was deemed insufficient for accurately predicting survival in COVID-19 patients requiring VA-ECMO treatment.Further investigation is needed to determine the most appropriate timing and indication for MCS in COVID-19 patients based on survival reports.